Weight loss in a cardiovascular trial population identifies people at future risk of dementia

Abstract Introduction Populations at increased risk of dementia need to be identified for well‐powered trials of preventive interventions. Weight loss, which often occurs in pre‐clinical dementia, could identify a population at sufficiently high dementia risk. Methods In 12,975 survivors in the Heart Protection Study statin trial of people with, or at high risk of, cardiovascular disease, the association of weight change over 5 years during the trial with post‐trial dementia recorded in electronic hospital admission and death records (n = 784) was assessed, after adjustment for age, sex, treatment allocation, and deprivation measures. Results Among the 60% without substantial weight gain (≤2 kg weight gain), each 1 kg weight loss was associated with a risk ratio for dementia of 1.04 (95% confidence interval, 1.02–1.07). Weight loss ≥4 kg and cognitive function below the mean identified participants aged ≥67 years with a 13% 10‐year dementia risk. Discussion The combination of weight loss and high vascular risk identified individuals at high risk of dementia who could be recruited to dementia prevention trials.

Power of a randomized trial in 10,000 participants to detect a 20% proportional 4 reduction in dementia incidence with treatment, according to the proportion of control participants getting dementia Table S2 International Classification of Disease (ICD-10) codes used for dementia 5 Table S3 Boundaries of the fifths of weight and body mass index measures within 6 each sex Table S4 Factors available for selection in the stepwise model of incidence of first 7 recorded dementia post-trial Table S5 Availability of factors other than age, sex and cognitive function terms in 9 three published dementia risk scores in Heart Protection Study (HPS) data Table S6 Incidence of first recorded dementia and death before recorded dementia in 11 the Heart Protection Study (HPS) during 0-9 years post-trial by age at final in-trial follow-up and risk group

Supplementary methods
To estimate the number of dementia cases not identified through linkage to hospital admissions (secondary care) that might be identified through primary care data, a support analysis was conducted using data from 230,685 participants in the UK Biobank prospective study who were linked to both NHS Digital Hospital Episode Statistics (as available in the Heart Protection Study) and Primary care data [1,2].
Follow-up data were censored at 14 June 2016, the last date that all sources of primary and secondary care data appeared to be complete (in data available for non-COVID-19 research), giving a mean follow-up of 7.3 years. First occurrence of dementia in primary care was defined using events in the UK Biobank first occurrence dataset where that earliest occurrence was from primary data records.
This dataset defined dementia as ICD-10 codes F00, F01, F02, F03 or G30 (which is very similar to the definition used in the present study). Dementia in secondary care/death records was defined using the same codes. Participants with dementia first recorded prior to baseline were excluded from the analysis (n=123). The subset of participants with myocardial infarction, stroke, transient ischaemic attack, angina, medically lowered blood pressure, revascularisation or diabetes at baseline were regarded as 'cardiovascular trial like' and therefore should be broadly similar to those in the Heart Protection Study.
The frequency of dementia in secondary care data, in primary care data as well, and alone, and in primary care data alone with at least 2 years of subsequent follow-up, was tabulated by age (<60, ≥60 years) and cardiovascular status.        Abbreviations: py = person years at risk The data line for age<67 years is shown in grey because these participants have not been included in the totals below (as their rate of dementia is too low). * Among the 71.5% of the 8014 participants in this table that had APOE genotyping * Follow-up is censored at the earliest of loss to follow-up from secondary care, primary care or death. † With prior myocardial infarction, stroke, transient ischaemic attack, angina, medically lowered blood pressure, revascularisation or diabetes at baseline. ‡ In this table, primary care data are taken from the first occurrence data fields whereas secondary care/death record data are taken from the hospital inpatient data and/or death certificates. Of 1029 dementias recorded in the first occurrence data, 267 were from primary care only, 140 were from primary care and other sources, 539 were from hospital admissions data only, 73 were from hospital admissions and other sources, 9 were from death records only, 1 was from death records and other sources. Age is at baseline. SE=Standard error Overall 769 cases of dementia were identified in secondary care and a further 260 were identified only in primary care. 156 cases identified in primary care with at least 2 years subsequent secondary care/death follow-up had not been identified in secondary care/death records within 2 years. Thus, an additional 156/769 (20%) of dementia cases may remain undetected by hospital admission diagnoses 2 years after primary care diagnosis. The pattern was similar in the different age and cardiovascular status strata.  Hazard ratio (95% CI) per 1kg/m 2 BMI loss over the three fifths with BMI loss or little change Figure S2: Associations of different body mass index (BMI) measures with the incidence of first recorded dementia post-trial, after standard adjustment. Number of dementia cases shown below each square. The lines displayed in the panels reflect data-driven summaries of the observed patterns. In the first two panels, the solid line shows the trend over the three fifths with BMI loss or little change and the dotted line shows the continuation of this line. *Using the mean BMI measure in each group as exposure dose   Figure S3: Associations of different systolic blood pressure (SBP) measures with the incidence of first recorded dementia post-trial, after standard adjustment. The ten participants (0.08%) with missing baseline or follow-up SBP are excluded from the analysis. Number of dementia cases shown below each square. The lines displayed in the panels reflect data-driven summaries of the observed patterns. In the first two panels, the solid line shows the trend over the three fifths with SBP loss and the dotted line shows the continuation of this line. *Using the mean SBP measure in each group as exposure dose      Figure S5: Association of APOE genotype with the incidence of first recorded dementia post-trial, cognitive z-score and weight change.